Using adult care visits to diagnose HIV infection in children, Burkina Faso

Abstract Objective To estimate the feasibility, positivity rate and cost of offering child testing for human immunodeficiency virus (HIV) to mothers living with HIV attending outpatient clinics in Burkina Faso. Methods We conducted this implementation study in nine outpatient clinics between October 2021 and June 2022. We identified all women ≤ 45 years who were attending these clinics for their routine HIV care and who had at least one living child aged between 18 months and 5 years whose HIV status was not known. We offered these mothers an HIV test for their child at their next outpatient visit. We calculated intervention uptake, HIV positivity rate and costs. Findings Of 799 eligible children, we tested 663 (83.0%) and identified 16 new HIV infections: 2.5% (95% confidence interval, CI: 1.5–4.1). Compared with HIV-negative children, significantly more HIV-infected children were breastfed beyond 12 months (P-value: 0.003) and they had not been tested before (P-value: 0.003). A significantly greater proportion of mothers of HIV-infected children were unaware of the availability of child testing at 18 months (P-value: < 0.001) and had more recently learnt their HIV status (P-value: 0.01) than mothers of HIV-negative children. The intervention cost 98.1 United States dollars for one child testing HIV-positive. Barriers to implementing this strategy included shortages of HIV tests, increased workload for health-care workers and difficulty accessing children not living with their mothers. Conclusion Testing HIV-exposed children through their mothers in outpatient clinics is feasible and effective in a low HIV-prevalence setting such as Burkina Faso. Implementation of this strategy to detect undiagnosed HIV-infected children is recommended.


Introduction
Despite great improvements in the response to human immunodeficiency virus (HIV), the 90-90-90 targets of the Joint United Nations Programme on HIV and AIDS (acquired immunodeficiency syndrome) for 2020 were not met in most countries in sub-Saharan Africa.For the first of these targets -by 2020, 90% of all people living with HIV will know their HIV status -an estimated 90% (95% confidence interval, CI: 73-98) of adults ≥ 15 years infected with HIV knew their status in southern and eastern Africa; this figure was 81% (95% CI: 67-98) in western and central Africa. 1 These figures fall to 65% (95% CI: 46-80) and 35% (95% CI: 26-47), respectively, for children aged 0-14 years. 2 This large gap between children and adults highlights important failures in HIV testing during the period of HIV exposure in utero to the end of breastfeeding.
The World Health Organization (WHO) recommends that infants exposed to HIV have nucleic acid testing by 4-8 weeks of age (early infant diagnosis), with a final diagnosis made at 18 months or 3 months after breastfeeding cessation, whichever is the most appropriate. 3Testing for early infant diagnosis is low, especially in western and central Africa where only 33% (95% CI: 25-47) of infants exposed to HIV are diagnosed by 8 weeks. 4Poor access to molecular testing and shortages of tests or reagents are common reasons for this situation. 5The final diagnosis is crucial and is often the last testing opportunity for HIV-exposed children.Although the 18-month testing can be done with a simple serological test, compliance is still low in sub-Saharan Africa, around 50% overall. 6,7Without diagnosis and treatment, an estimated 52.5% of HIV-infected children will die by the age of 2 years. 80][11] Factors associated with poor testing uptake include loss to follow-up of mothers or infants from health facilities, shortages in diagnostic reagents and delayed results. 5rovider-initiated testing and counselling and index family testing can help increase diagnosis of HIV in infants. 12,13ndex family testing in high-prevalence settings in priority Bull World Health Organ 2024;102:187-195| doi: http://dx.doi.org/10.2471/BLT.23.289606   Souleymane Tassembédo et al. 11,[14][15][16][17][18] has relied mainly on fathers as the index case and targeted mostly adolescents.In Kenya, 2848 children aged 0-14 years whose mothers and fathers were newly enrolled in HIV care were tested, 127 (4.5%) of whom were newly diagnosed with HIV. 19ew studies on testing children through their index parents have been conducted in west and central Africa. 1 In Cameroon, mothers and fathers attending clinics for antiretroviral therapy (ART) were offered testing for their children aged 0-15 years. 10Only 46.2% (571/1236) of the parents had at least one child tested, with better acceptance when the mother was the index case.In Nigeria, parents contacted at various entry points were offered HIV testing for their children aged 0-15 years.Testing uptake reached 83.6% (1822/2180), and 3.5% (24/683) of the children were HIV-positive. 11n west Africa, HIV is more prevalent in women and they have better access to screening and treatment.Women are also more adherent to follow-up than men, [20][21][22][23] and children from index mothers are tested more frequently. 10onsequently, a case-finding strategy with women as the index case may be more appropriate in west Africa.

Research countries of the Global plan towards the elimination of new HIV infections among children by 2015 and keeping their mothers alive
In this study, we estimated the feasibility, HIV positivity rate and cost of a strategy to test children for HIV in Burkina Faso by targeting women of childbearing age who were routinely followed up in outpatient clinics as index cases.

Design and setting
We used an effectiveness-implementation hybrid trial type 1 study design. 24urkina Faso has a low HIV prevalence estimated at 0.7% (95% CI: 0.5-0.8) in adults aged 15-49 years. 1 The mother to child transmission (MTCT) rate, including through breastfeeding, was estimated at 12% (95% CI: 9.2-16.1) in 2020. 1 Coverage of early infant diagnosis estimated from national programme data is 10% (95% CI: 8.4-12.8); 1 no data are available on the 18-month HIV test coverage.The prevention of mother to child transmission (PMTCT) programme covers care for HIV-infected mothers and infants at maternal and child units at Centres de Santé et de Promotion Sociale (lowest level of health-care services) until the child is 2 years.After this age, the child exits the PMTCT programme and is referred to a paediatric HIV clinic for care.
We implemented our strategy in the two cities of Burkina Faso, Ouagadougou and Bobo-Dioulasso, between October 2021 and June 2022.We recruited participants from nine public outpatient clinics at two tertiary hospitals (Centre Hospitalo-Universitaire Yalgado Ouedraogo and Centre Hospitalo-Universitaire Souro Sanou), three district hospitals (Do, Dafra and Boulmiougou) and four community clinics (Centre Oasis, Clinique Yerelon Ouaga, Clinique Yerelon Bobo-Dioulasso and Centre REVS Plus Bobo-Dioulasso).We chose these clinics to match the local HIV care situation and include all levels of the health system.The usual staff at these clinics implemented the strategy.When we started this study, HIV clinics had no testing capacity because their mandate was only to treat people referred with a confirmed HIV diagnosis.The National AIDS Control Programme provided testing kits, and we trained staff in their use for children.

Population and sample size
The study population was women living with HIV followed at the outpatient clinics, and their biological children aged 18 months to 5 years whose HIV status was unknown.In this study, female sex was assessed by the individual's selfidentification as a mother.No attempt to assess gender was made.
Based on a 2% positivity rate in exposed children older than 18 months in Burkina Faso, 25 a 10% non-response rate, 1% precision and a 5% uncertainty level, the sample size needed was 753 children.

Implementation
We identified all women followed at the nine sites.We then contacted the women aged 45 years or younger by telephone or at the clinic to determine whether they had at least one living child aged between 18 months and 5 years whose HIV status was not known.We offered mothers with at least one eligible child an HIV diagnosis for their child, and asked them to bring the child at their next usual outpatient visit, or at an earlier time if they preferred.Additionally, we conducted twice-weekly counselling sessions on postnatal MTCT of HIV and its prevention to educate women and encourage child testing.We excluded women without a child in this age group or who had a child whose HIV status was known.
After the mother gave her consent to participate, the clinic nurse recorded the mother's sociodemographic characteristics, HIV testing history of her child, and infant feeding history using a standardized questionnaire on a tablet.
All eligible children underwent HIV serological screening according to the national protocol.Clinic staff tested the children using a rapid test (Alere Determine HIV-1/2 Ab, Abbott, Chiba, Japan).If the test was negative, the child was considered HIV-negative.If the test was positive, staff did a second test (OnSite ® HIV 1/2 Ab Plus Combo Rapid Test, CTK Biotech, Poway, United States of America) to confirm HIV infection and determine the type (HIV-1 or HIV-2 or dual reactivity).For indeterminate results, clinic staff offered repeat testing 1 month later or a nucleic acid test whenever possible.Children who were still breastfeeding at the time of the study who tested negative at the first visit were assessed again at the next routine visit until 3 months after breastfeeding cessation.
The staff and mothers received no financial compensation, as the child testing was during a routine maternal visit for HIV care and took little time.

Outcomes
We determined feasibility of the strategy by assessing the difficulties encountered by HIV services in implementing the strategy and the uptake of the intervention by the mothers.We measured uptake as the proportion of mothers who brought their children for testing of the total number of mothers contacted.
We estimated the HIV positivity rate as the proportion of children who tested HIV-positive of all children tested.
We evaluated the acceptability of the strategy during on-site monitoring visits, by asking health-care workers to provide feedback on the challenges encountered in implementing the strategy.
To estimate the financial costs of the strategy, we used data from the National AIDS Control Programme.We categorized costs as capital or recurrent.Recurrent costs included supplies (testing kits, gloves, alcohol, swabs and

Statistical analysis
We summarized the characteristics of the mothers and children as proportions with 95% binomial CIs and as medians and interquartile ranges (IQR) for categorical and continuous variables, respectively.
We compared the characteristics of the children found positive and negative for HIV using the Pearson χ 2 test or Fisher exact test for categorical variables, and the Mann-Whitney U-test for continuous variables.
We used Stata, version 16.0 (Stata-Corp, College Station, USA) for data analyses.

Ethical considerations
The Burkina Faso Health Research Ethics Committee approved the study protocol.All women who agreed to participate signed an informed consent form.We referred HIV-infected children to an appropriate HIV paediatric care centre.

Results
Between October 2021 and March 2022, we assessed 2554 women living with HIV for participation in the study.Of these women, 799 had eligible children and 789 agreed to participate (response rate 98.7%).Of the 789 mothers, 663 (84.0%) brought their children for HIV testing.We excluded 27 children from the analysis (Fig. 1).

Participant characteristics
The median maternal age of the mothers was 37 years (IQR: 32-41 years), and 43.1% (274/636) had no formal education.Most mothers (83.5%; 531/636) were living as a couple (with a spouse or partner) and 89.1% (567/636) said that they had disclosed their HIV status to their partner and/or family.The median age of the children was 3 years (IQR: 2-4 years) and 52.8% (336/636) were female.Breastfeeding had stopped after 12 months for 55.3% (332/600) of the children, and 41.3% (263/636) of the mothers reported that their child had tested negative for HIV before or at 12 months of age (Table 1).

HIV-positive children
Among the 636 children exposed to HIV, 16 were HIV-positive, giving an HIV prevalence of 2.5% (95% CI: 1.5-4.1).The mothers of the HIV-positive children were significantly younger, and had been diagnosed with HIV and started treatment more recently than mothers of uninfected children.Compared with the HIV-negative children, a significantly greater proportion of HIV-positive children had been breastfed beyond 12 months (P-value: 0.003).Only 37.5% (6/16) of mothers of HIVinfected children were aware of systematic HIV testing at 18 months for their child compared with 85.5% (530/620) of other mothers (P-value: < 0.001).Additionally, a significantly greater proportion of mothers of HIV-infected children reported missing ART during pregnancy (P-value: 0.02; Table 2).
Of the 16 HIV-infected children, 10 were started on ART on the same day as diagnosis, five started within 1 week and one started 1 month after the diagnosis.

Feasibility of the intervention
The challenges of the intervention reported by the clinic staff included a shortage of HIV tests, high turnaround of health workers and increased workload as a result of the intervention.Some staff were also uncomfortable using tablets to record the participants' data.The challenges reported by mothers were transportation costs to return with their child; the fact that their child was not living with them (living with their fathers, grandparents or other relatives); and their child was at school.
Recruitment and testing of children was slower at the tertiary hospital outpatient clinics than the community-based primary health care facilities.

Cost of the intervention
The total intervention cost for the 636 children in this analysis was US$ 1569.7, with telephone costs to contact mothers accounting for the largest share (52.6%;US$ 825.0).The average costs were US$ 2.4 for testing one child, and US$ 98.1 per child testing positive for HIV (Table 3).

Discussion
Our strategy of testing children of HIV-infected mothers routinely followed at outpatient clinics was efficient at identifying children with HIV whose status was unknown.Without this intervention, these children would either never have been diagnosed or would survival rate of 50% at 2 years and 20% at 5 years, 8 at least two to three times as many children are likely to have died before we could diagnose them.This finding emphasizes the need for systematic identification of eligible children aged 18 months to 2 years in women attending HIV care centres.Efforts are also needed to identify undiagnosed mothers who become infected after delivery or breastfeeding.Importantly, our real-life intervention was feasible and acceptable.The 98.7% acceptance rate of the mothers was higher than other studies with index parents including mothers: pooled estimate 51.7% (95% CI: 10.4-92.9) in sub-Saharan Africa; 27 90.7%(807/890) in Nigeria; 11 and 93.5% (431/461) in Malawi. 18This finding suggests that an HIV medical consultation may avoid potential stigma reported in other contexts.However, 15.7% of our mothers did not bring their children for HIV testing.The reasons for this situation include: child no longer living with their mother; mother's unwillingness to have their child tested; approval needed from the father whom the mother was reluctant to ask; father's refusal to allow their child to be tested; lack of money for transportation; and remoteness of the health facility. 28The short study duration did not allow us to assess if some of these mothers could have overcome these difficulties and eventually had their child tested.
The fact that district and tertiary hospitals had more difficulty recruiting and testing children than communitybased clinics at the beginning of the study was expected, as the communitybased clinics have extensive experience in HIV testing and counselling.Therefore, these clinics were better prepared to start screening children.District and tertiary hospital outpatient clinics focus on care not testing, particularly for children.Some staff found the use of tablets for data collection difficult.However, such data are not required for our strategy to be routinely adopted.
In our study, 83.0% of eligible children were tested, which is higher than a study in Kenya in which parents at outpatient clinics were given incentives to bring their child for testing. 15Child testing uptake was only 33.3% (30/90) for the group with no incentive, and 61.4% (54/88) for the group given the highest incentive (US$ 10). 15A study in Nigeria in which child testing was performed at the facility level reported a similar testing rate (85.9%; 693/807) to our study. 11he difficulty of reaching children not living with their mothers requires Identifying HIV-infected children, Burkina Faso addressing.Home testing may be an option but this approach has limitations because of frequent non-disclosure of the mother's HIV status to her partner or family; fear that the child will test HIV-positive; and stigma. 29ther studies in Africa have assessed whether community and home-based testing could improve HIV testing in children.A study in Zimbabwe offering the choice between the two places for testing reported HIV testing uptake was only 60% (3638/6062) and significantly higher with home-based testing. 17However, in Kenya, most parents said they preferred clinic-based testing (76.6%; 377/492) to home-based testing. 30Home testing was feasible in eastern Africa and offered flexible options to parents, but this approach requires considerable resources for a relatively poor added value in terms of HIV testing.In addi-

Research
tion, home-based testing may be more challenging in Burkina Faso because of the high level of stigma in having an HIV-infected child. 29Importantly, our findings confirm that facility-based testing allows ART to be started quickly as recommended by WHO. 31 All children diagnosed with HIV in our study started ART shortly after the HIV diagnosis.
Travel time, high costs 17 and low educational level 10,32 may be barriers to facility-based testing.Our approach, nested within the mother's routine HIV care visit, eliminates these difficulties.Of note, having community health workers and health-care providers explain the course of HIV and the importance of child testing likely contributed to our high acceptance rate.
As expected, the characteristics of the children infected with HIV and their mothers revealed a certain risk profile: younger age of mother; shorter period since mother started ART; poorer adherence to ART by the mother; and less awareness of the 18-month test.This last finding highlights the need to inform mothers of this final HIV test as part of the PMTCT programme.In addition, breastfeeding duration was longer in HIV-infected children, suggesting that some infections may have occurred after 12-18 months, as reported previously in Burkina Faso and other countries. 25A final HIV test for all children exposed to the virus whenever their exposure ends, for example when they stop breastfeeding whatever the age, is therefore vital.
The average cost for testing children seems feasible for the national AIDS control programme (US$ 2.5) and is lower than provider-initiated testing and counselling in South Africa (US$ 4.7). 33ur study has several limitations.Some HIV-infected children identified may have been previously reported by their mothers.We believe this bias was unlikely as we gave no incentive to the mother to have her child tested.In addition, we did not achieve the calculated sample size because the number of women with an eligible child was lower than we expected, which may have reduced the precision of our estimates.Finally, we did the cost assessment retrospectively as we did not originally plan to do one.However, we had precise records of costs so we believe our estimates are accurate.
To conclude, identifying undiagnosed children with HIV through their mothers' routine follow-up in HIV outpatient clinics was feasible and effective in a typical west Afri-can context.Importantly, testing in a health facility enabled rapid initiation of ART for all HIV-infected children.

Fig. 1 .
Fig. 1.Flowchart of recruitment of women and children to diagnose HIV infection in children, Burkina Faso, 2021-2022

Table 2 . Characteristics of the children by HIV status, Burkina Faso, 2021-2022
ART: antiretroviral therapy; HIV: human immunodeficiency virus; IQR: interquartile range.a Data were missing for one child.b Data were missing for 35 children.